Ocular surface adverse events of systemic epidermal growth factor receptor inhibitors (EGFRi): A prospective trial.

PURPOSE: Controversy exists regarding the safety of agents that systemically inhibit epidermal growth factor receptor (EGFRi) in oncologic patients in terms of toxicity to the ocular surface. We performed a prospective clinical study comparing the ocular surface toxicity of systemic EGFRi between a case and a control group. METHODS: Patients with lung or colon cancer were divided in two groups: 25 patients treated with systemic EGFRi and 25 control patients without EGFRi treatment. Patients in both groups were chemotherapy naive. Four visits were scheduled in a one year period comparing signs and symptoms in terms of symptom questionnaires (SIDEQ, OSDI and AVS), corneal fluorescein staining (Oxford test), tear production (Schirmer's test) and a quantitative evaluation of conjunctival chemosis and hyperemia. Basal epithelial cell density (CEBD) and corneal subepithelial nerve fiber density (CNFD) were measured and compared using confocal microscopy (Heidelberg Engineering, Germany). The differences in each variable were compared with the analysis of variance (ANOVA). A P value<0.05 was considered significant for all comparisons. RESULTS: No statistically significant differences were found between patients under EGFRi treatment and the age-matched controls in the variables analyzed. When cases and controls were evaluated separately, the case group showed a significantly worse progression of signs (chemosis score, CFS, Schirmer's) as well as in terms of CEBD and CNFD (all P<0.05). CONCLUSION: Systemic EGFRi may increase dry eye signs as well as decrease CEBD and CNFD. This study may help us to understand the true toxicity of EGFRi to the ocular surface.

[Influenza A(H1N1)v virus infection in infants less than 6 months of age in southwestern France]. / Grippe A(H1N1)v chez les nourrissons de moins de 6 mois en Aquitaine.

OBJECTIVE: We evaluated the severity of influenza A(H1N1)v clinical forms among infants less than 6 months of age. This population group was considered a high-risk group, so all people around them should be vaccinated first. PATIENTS AND METHODS: In south-western France in Aquitaine, we collected all infants less than 6 months of age during a period between the 6th September 2009 and the 6th January 2010 with influenza A(H1N1)v confirmed by PCR. For each of them, the risk factors, clinical presentation, hospitalization, and course of, the disease were identified. We compared two groups: children under 3 months and infants aged 3-6 months. RESULTS: We identified 74 infants. The average age was 3 months. Sixteen infants had at least 1 risk factor: 9 respiratory diseases (12%), 8 born prematurely (but there was no preterm baby under 33 weeks); one infant presented a cardiac disease, and another 1 epilepsy. Five infants showed no fever, 73% had cough, and 24% had gastro-intestinal symptoms. Infants under 3 months of age presented less cough (P<0.025) and fewer gastro-intestinal symptoms (P<0.01) than older ones. Only 5 infants needed oxygen and 4 presented pneumonia. Forty-eight infants were hospitalized, including 1 in intensive care, with a median duration of 3 days. Forty-five percent spent 2 days or less in the hospital. Infants under 3 months of age were more often hospitalized (P<0.001). CONCLUSIONS: Infants under 6 months of age did not present a severe form of influenza A(H1N1)v. Infants under 3 months of age were less symptomatic than older infants and were often hospitalized, but hospital stays were short with a good outcome.

[First and second line antibiotic therapy for bacterial meningitis in infants and children]. / Modalités de l'antibiothérapie (initiale et ultérieure) chez l'enfant d'un à trois mois et de plus de trois mois (examen direct positif et examen direct négatif).

The potential severity of meningitis in infants and children requires an optimized initial empirical therapy, mainly based on direct cerebro spinal fluid (CSF) examination, and rapid therapeutic adaptation according to bacterial identification and susceptibility. Combination treatment including cefotaxim (300 mg/kg per day) or ceftriaxone (100mg/kg per day) and vancomycine (60 mg/kg per day) remains the standard first line if pneumococcal meningitis cannot be ruled out. A simple treatment with third generation cephalosporin can be used for Neisseria meningitidis or Haemophilus influenzae meningitis, aminoglycosides must be added in case of Enterobacteriacae, mainly before 3 months of age. Second line antibiotic therapy is adapted according to the clinical and bacteriological response on Day 2. When the minimal inhibitory concentration (MIC) of pneumococcal strain is less than 0.5mg/L, third generation cephalosporin should be continued alone for a total of 10 days. In other cases, a second lumbar puncture is necessary and the initial regimen, with or without rifampicin combination, should be used for 14 days. Amoxicillin during 3 weeks, associated with gentamycin or cotrimoxazole is recommended for listeriosis.

Mass detection on mammograms: influence of signal shape uncertainty on human and model observers.

We studied the influence of signal variability on human and model observers for detection tasks with realistic simulated masses superimposed on real patient mammographic backgrounds and synthesized mammographic backgrounds (clustered lumpy backgrounds, CLB). Results under the signal-known-exactly (SKE) paradigm were compared with signal-known-statistically (SKS) tasks for which the observers did not have prior knowledge of the shape or size of the signal. Human observers' performance did not vary significantly when benign masses were superimposed on real images or on CLB. Uncertainty and variability in signal shape did not degrade human performance significantly compared with the SKE task, while variability in signal size did. Implementation of appropriate internal noise components allowed the fit of model observers to human performance.

[Neonatal infections of the bones and joints]. / Infections ostéoarticulaires du nouveau-né

Neonatal osteoarticular infections remain rare, with an estimated incidence of 1 to 3 cases per 1000 admissions to Neonatal Intensive Care Units. It usually results from bacteraemia and may thus be induced by IV catheters. More rarely it is due to direct inoculation secondary to cutaneous damage, or extension of soft tissue infection. The particularity of bone vascularization in the newborn explains the frequency of abscess formation in the periosteum or in soft tissues. The main pathogen involved is S. aureus (3/4 of cases), followed by group B streptococci and enterobacteriacae. Infection consists mainly of localised and slowly progressing abscesses. However, multifocal and severe infection is possible, in particular when caused by an IV catheter. Ultrasonography is the best initial investigation, possibly leading to surgical care. Medical treatment must include 2 synergistic antistaphyloccocal antibiotics, possibly associated with cefotaxime. The outcome is generally favorable, but orthopaedic consequences may emerge if the growth plate is involved. Rare specific causes, such as syphilis or tuberculosis, should also be evoked, but the clinical context is generally helpful for the diagnosis.

[Multifocal infection due to Mycobacterium intracellulare: first case of interferon gamma receptor partial dominant deficiency in tropical French territory]. / Infection multifocale à Mycobacterium intracellulare: premier cas de déficit partiel dominant du récepteur de l'interféron gamma en milieu tropical français.

Nontuberculous mycobacterial infections are rare in immunocompetent children, and usually present as adenitis. We report a case of a 6-year-old girl with a multifocal chronic osteomyelitis and pulmonary localisation due to Mycobacterium intracellulare associated with an autosomal dominant mutation of interferon gamma receptor 1 gene (INFGR1) leading to a syndrome of mendelian predisposition to mycobacteria infections by partial deficiency of intracellular signalisation of gamma interferon. This child has been cured with anti-mycobacteria drugs and gamma interferon. This report focus on the importance of looking for a susceptibility of the host to infectious diseases, which can lead to a specific treatment. As far as we know, this is the first case described in a tropical area.

[Chlamydia infection in neonates and infants]. / Infections à chlamydia du nouveau-né et du nourrisson.

Incidence of chlamydial infection depends on maternal colonization during pregnancy, which is different in each population. The transmission is not obligatory but when present, it occurs at birth through the genital tractus. Chlamydia trachomatis infection is the first cause of neonatal conjunctivitis, with no influence of eye lotion application at birth. C. trachomatis is also responsible for interstitial pneumonia with possible consequences on the lung function. The laboratory diagnosis relies on the identification of intracellular bacteria in patient samples by the mean of culture or PCR. Systemic antibiotherapy by macrolides is always necessary, with local application in the case of conjunctivitis. The key point is the detection of colonization of pregnant women with identified risk factors. In positive case, oral treatment of both parents is recommended.

Metástasis ósea como primera manifestación de un hepatocarcinoma / Bone metastases as the first manifestation of hepatocarcinoma

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DSC1 channels are expressed in both the central and the peripheral nervous system of adult Drosophila melanogaster.

DSC1 encodes a putative voltage-sensitive sodium channel alpha subunit in Drosophila melanogaster. We generated polyclonal antibodies raised against part of the DSC1 sequence to characterize the size and the distribution of these channels in the adult fly. Immunoblotting experiments indicated that the protein has a molecular weight of about 270 kDa. We also showed that DSC1 channels are found only in the neurons of the fly. The density of channels was high in synaptic regions and in most of the axonal processes that connect the various structures of the CNS. No signal was observed in the cortical cell bodies where the para channels are mainly present. The most striking result concerns the widespread distribution of DSC1 channels in the PNS, as confirmed by experiments done with the monoclonal antibody 22C10. These results strongly suggest that DSC1 and para channels may have complementary roles, at least in the adult stage.

Expression and distribution of voltage-sensitive sodium channels in pyrethroid-susceptible and pyrethroid-resistant Musca domestica.

Knockdown resistance (kdr) to pyrethroid insecticides has been found in numerous insect species. kdr causes nerve insensitivity by altering the primary target of these insecticides, the voltage-sensitive sodium channel. In Musca domestica, cloning and sequencing of susceptible, kdr, and super-kdr alleles of the sodium channel gene (Msc) homologous to the Drosophila melanogaster para channel gene has revealed point mutations. The conservation of the nature and of the position of these mutations strongly suggests a role in the kdr mechanism. To determine if these mutations are associated with modifications of channel expression in adult flies, we investigated the localization of the Msc transcripts, and the size and the tissue distribution of the channel protein in pyrethroid-susceptible and super-kdr strains. Msc channels were mainly found in the cortical regions of the central nervous system with additional labeling in some neuronal processes and in the eyes. No qualitative or quantitative difference was observed between the strains. In immunoblotting experiments, anti-Msc antibodies bound to only one polypeptide of 260 kDa in adult brain. No differences were found in antibody staining between susceptible and pyrethroid-resistant strains. These results were correlated with those on Drosophila melanogaster, for which two sodium channel genes have been identified.

Transcription analysis of the para gene by in situ hybridization and immunological characterization of its expression product in wild-type and mutant strains of Drosophila.

In Drosophila, the para gene has been shown to encode a functional voltage-dependent sodium channel. We used a cDNA clone to study the distribution of its transcripts by in situ mRNA hybridization on adult fly sections. These transcripts are found in cortical regions of the central nervous system and in the eyes. On immunoblots, antibodies raised against expression products of part of the gene recognize a polypeptide of M(r) approximately 270,000 in head membranes. Immunolocalization experiments indicate that anti-para antibodies bind to cortical regions of the brain and give heavy signals in the eyes. Immunohistochemistry was also performed on napts and seits1, two mutant Drosophila strains known to be defective in sodium channel activity. Only napts flies displayed a decrease in the expression of the para protein.